title: Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice.
abstract: The runt-domain transcription factor Runx3 plays crucial roles during development such as regulating gene expression. It has been shown that Runx3 is involved in neurogenesis, thymopoiesis and functions like a tumor suppressor. Runx3 null mouse die soon after birth as a result of multiple organ defects. Runx3 null mouse lung shows an abnormal phenotype and loss of Runx3 induced remodeling in the lung. Interestingly, lung adenocarcinoma is observed in Runx3 heterozygous mice at 18 months of age. During lung development various cellular and molecular events occur such as cell proliferation, cell death, differentiation and epithelial-mesenchymal transition (EMT). To understand the specific lethal events in Runx3 null mice, we examined cellular and molecular networks involved in EMT, and EMT inducers were quantified by RT-qPCR during lung development. Excessive EMT was observed in lungs at PN1 day in Runx3 null mice and PN18 months in Runx3 heterozygous mice. Pharmacologic inhibition of EMT was used to curb tumor progression. In this study, U0126 was injected to pregnant mouse for inhibition of pERK signaling. After U0126 treatment, life spans of newborn mice were increased and lung hyperplasia was partially rescued by down-regulated cell proliferation and EMT. Our data suggest that Runx3 is involved in crucial regulation of alveolar differentiation and tumor suppression in developing mouse lung.
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 project, Oral Science Research Center, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Jeong-Oh
authors.initials: JO
authors.lastname: Shin
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Cho
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hosoya
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Cho
authors.forename: You-Soub
authors.initials: YS
authors.lastname: Lee
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Suk-Chul
authors.initials: SC
authors.lastname: Bae
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008168:Lung / Q000002:abnormalities / Q000254:growth & development* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009570:Nitriles / Q000494:pharmacology; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D002070:Butadienes; D050677:Core Binding Factor Alpha 3 Subunit; D009570:Nitriles; D019892:eIF-2 Kinase; C493730:Runx3 protein, mouse; C113580:U 0126